2 Americans Share Nobel for Cell Studies
Two American researchers who discovered how most of the biochemical processes of life are regulated were named Monday to receive the 1992 Nobel Prize for physiology or medicine.
Edmond H. Fischer, 72, and Dr. Edwin G. Krebs, 74, both at the University of Washington, will share the $1.2-million award for their pioneering studies of how chemical reactions within cells are turned on and off. Fischer is a biochemist and Krebs and internist who practiced medicine in the Navy before taking up a research career.
Their work has helped researchers understand such disparate biological problems as how the drug cyclosporine prevents rejection of transplanted organs, why certain cancers develop, how hormones affect the body and how the body mobilizes sugar to produce energy.
In studies conducted nearly 40 years ago, Fischer and Krebs discovered that most processes within cells--ranging from fundamental metabolic reactions to the initiation of cancer--are triggered when key proteins are chemically activated by a process called phosphorylation. They were the first to identify and characterize an enzyme that carried out phosphorylation, and that discovery led to an explosion in knowledge about how cells grow, change, divide and die.
Phosphorylation “lies at the basis of all biological function,” said biochemist Dan Storm, a colleague of Fischer and Krebs at Washington. The process is so important, according to the Nobel citation, that fully 1% of the human genetic complement is devoted to blueprints for the production of the enzymes that carry out phosphorylation.
And because phosphorylation is involved in so many cellular processes, researchers hope that its manipulation may lead to new treatments for a variety of medical conditions. For example, by inhibiting phosphorylation, some anti-rejection drugs used in transplant operations block the activation of white blood cells that would attack the new organ. And many biologists believe that blocking phosphorylation in cancer cells could bring tumor growth to an abrupt halt.
“It may lead to totally different types of anti-cancer drugs,” Dr. Gosta Gahrton of the Karolinska Institutet in Stockholm said Monday during the press conference at which the award was announced.
The Nobel committee was unable to reach either researcher early Monday and both were informed of the award by U.S. news media. Krebs learned about it five hours after the announcement when an Associated Press photographer knocked on his door in Seattle to take his picture. Krebs, at home for the Columbus Day holiday, said he was hard of hearing and had not heard the downstairs telephone ringing. His wife and two daughters are vacationing in England.
He said he was “utterly surprised and in a state of disbelief.” In a later telephone conversation with the Nobel committee, he said, “It makes it all believable to hear it from you. I’m so delighted.”
Fischer said that he, too, was “totally overwhelmed. . . . It’s surprising because when you think of how many people are doing superb work in the field, you can think of literally dozens of other people who would deserve it.”
Their joint research began about 40 years ago, shortly after Fischer arrived at the University of Washington from his native Switzerland and learned that he and Krebs were investigating the same problem--how muscles obtain the energy to contract. “Krebs slapped me on the back and said, ‘Let’s take a crack at that problem,’ ” Fischer recalled Monday.
While searching for the energy source in muscles, they “happened to stumble on a reaction that regulates the activity of a muscle enzyme,” Fischer said. Initially, “we had no idea how widespread this reaction would be . . . whether it would be something very unique or very unimportant,” he said. But eventually it proved to be “one of the most important reactions by which cells are turned on and off.”
But Krebs and Fischer were ahead of their time, said biochemist Hans Wigzell of the Nobel committee. The scientific community did not begin to understand the significance of their work until 10 years later, in the mid-1970s.
“Then it took off like a rocket,” Wigzell said. “Now 10% of all biology articles in journals like Nature or Science deal with their field.”
Although the Nobel Prizes were originally established to honor research in the year before the award, such belated recognition of achievements as this year’s award has become more common.
Krebs and Fischer are now emeritus professors at the University of Washington, but they continue their research. Krebs is concentrating on hormonal regulation in diseases such as diabetes, while Fischer is studying the process of cell transformation in cancer research.
